DESCRIPTION: Airways hyperreactivity and inflammation are hallmarks of asthma. Although much speculation exists regarding the involvement of the airway circulation in asthma, the precise role of the bronchial circulation in modulating airways reactivity and inflammation is not clear. We've demonstrate previously that the bronchial circulation is essential in both delivering and clearing chemicals to and from airway smooth muscle. Controversy exists as to whether this circulatory bed, through engorgement and edema, can cause physica encroachment on the airway lumen and cause airflow obstruction. Although some experimental evidence exists for these physical processes exerted by the bronchial vascular network, the ability of bronchial vascular cells to influence airway smooth muscle tone is unstudied. Blood flow-induced stimulation of bronchial endothelium is likely an important mechanism to control regional perfusion and distribution of blood-borne substances. Furthermore, dilator substances released by the endothelium may diffuse to airway smooth muscle and affect airway tone. Inflammatory cell recruitment to the airway wall is generally assumed to be controlled by airway vascular endothelial adhesion, but, little in vivo data exists to support this assumption. Thus, in this application, we propose the following HYPOTHESIS: Th bronchial vascular endothelium is pivotal in determining the degree of airway smooth muscle tone and permissive in allowing airways inflammation. Experiment will be performed in anesthetized sheep in which the bronchial artery will be cannulated and perfused. Specific aims will determine 1) whether shear-induced release of endothelial-derived dilators (nitric oxide and prostacyclin), alter blood flow distribution and/or decrease airway smooth muscle tone; 2) whether shear stress influences leukocyte influx into the airway; and 3) whether in an inflammatory state, bronchial vascular engorgement and edema alter airway dimensions.